Adoptive cell transfer (ACT) is a promising immunotherapeutic approach for cancer treatment. During ACT, if a patient is subjected to lymphodepletion prior to cell transfer, there is an observed improvement in a patient’s response to treatment. However, lymphodepletion is associated with detrimental effects, including severe immune dysfunction that persists after treatment.

Antibody drug conjugates (ADC) can demonstrate high efficacy as cancer therapeutics, however, much more can be done to improve their efficacy and safety profile. Site-specific antibody drug conjugation is a promising way to do this. Scientists at the NCI’s Laboratory of Experimental Immunology have identified a fully human monoclonal antibody, m860, that binds to cell surface-associated Her2 with affinity comparable to that of Trastuzumab (Herceptin) but to a different epitope.

Nitric oxide (NO) has a broad spectrum of actions in physiological and pathological processes.  NO-donor drugs have shown therapeutic effect in several cancer types by inducing apoptosis but the concentrations required have suggested limited clinical applicability.  For cancers such as non-small cell lung cancer where most therapies are not curative, there remains a need for effective treatments. 

Soluble forms of human CD4 (sCD4) inhibit HIV-1 entry into immune cells.  Different forms of sCD4 and their fusion proteins have been extensively studied as promising HIV-1 inhibitors – including in animal models and clinical trials.  However, they have not been successful in human studies due to their transient efficacy.  sCD4 is also known to interact with class II major histocompatibility complex (MHCII) and, at low concentrations, could enhance HIV-1 infectivity. 

Aberrant function of the WNT-b-catenin pathway is a common underlying cause of tumorigenesis.  Despite the attractiveness of the WNT-b-catenin pathway as a therapeutic target, WNT dependent cell signaling is also crucial for normal tissue development, and is ubiquitous in all organs.  As a result, WNT-b-catenin pathway inhibitors cause many side effects and fail to meet FDA safety standards.  A more targeted approach is needed to develop safe and effective WNT signaling inhibitors.

Integrase strand transfer inhibitors (“INSTIs”) are currently in use as a component of prophylactic antiretroviral therapy for preventing HIV-1 infection from progressing to AIDS. Three INSTIs are approved by the FDA for inclusion in antiretroviral regiments: raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG). Clinicians have already identified several HIV-1 integrase mutations that confer resistance to RAL and EVG, and additional mutations that confer resistance to all three INSTIs has been identified in the laboratory.

The development of an effective HIV vaccine has been an ongoing area of research. High variability in HIV-1 virus strains, however,  represents a major challenge.  Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV.  Two major hurdles to overcome are immunodominance and sequence diversity. Researchers at the National Cancer Institute (NCI) have developed a vaccine that overcomes these major hurdles by utilizing a strategy that identifies conserved regions of the virus and exploits them for use in a targeted therapy.

 A number of factors can play a detrimental role in the process of wound healing such as poor nutritional status, smoking, various drugs, cancer, and diabetes.  Wound healing impairment is a challenging clinical problem with no efficacious treatments currently available.  Nitric oxide (NO) has been shown to play a role in the process of wound healing by promoting both the proliferative and remodeling phases of healing. 

Melanoma is an aggressive form of skin cancer that commonly becomes metastatic, spreading to nearby tissue or other parts of the body, including distant skin or subcutaneous sites such as the lungs, liver, brain, or bone. Metastatic melanoma is very drug resistant and difficult to treat, and therefore, the prognosis for these patients is poor. There is a need for effective therapies for aggressive melanoma and other drug-resistant solid cancers. 

Currently available topical antibiotic formulations effectively eliminate bacteria at a wound site. Eliminating bacteria in the wound also eliminates the molecular signals present in bacterial DNA that stimulate the immune system's wound healing processes. Without these signals, the rate of wound healing is diminished.